Immune Defense against Bacterial Pathogens

Immune Defense against Bacterial Pathogens: Innate Immunity

Innate Immunity is a form of non specific host defense against invading bacteria. It is natural or “innate” to the host, depending, in part, on genetics. Innate defense mechanisms are constitutive to the host, meaning they are continually ready to respond to invasion and do not require a period of time for induction.

Categories of Innate or Nonspecific Immunity

1. Differences in susceptibility to certain pathogens 2. Anatomical defense 3. Tissue bactericides, including complement 4. Microbial antagonism 5. Inflammation (ability to undergo an inflammatory response) 6. Phagocytosis

The first four categories are generally considered non cellular defenses.Inflammation and Phagocytosis are forms of cellular defense.

1.Differences in Susceptibility of Animal Hosts to Microbial Pathogens (Natural Immunity)

Natural immunity or resistance is based on the genetics of the host. There are two aspects: 1) resistance among all members of a species, called species resistance ；

2) resistance within members of the same animal species, called individual resistance.

Species resistance

1 ） Absence of specific tissue or cellular receptors for attachment (colonization) by the pathogen.

2)Temperature of the host and ability of pathogen to grow.

3)Lack of the exact nutritional requirements to support the growth of the pathogen.

4)Lack of a target site for a microbial toxin.

Individual resistance

Age. The changes in immunological system and normal flora .

Sex. It could be due to anatomical structure related to sex , and possibly the effects of sex hormones on infections.

Stress. The best explanation is that in time of stress the output of cortisone from the adrenal cortex is increased. This suppresses the inflammatory processes .the overall effect may be harmful. There are also a number of relationships between stress-related hormones and the functioning of the immune defenses.

Diet, malnutrition. Infections may be linked with vitamin and protein deficiencies. Also, overfed and obese animals are more susceptible to infection.

Intercurrent disease or trauma. The normal defenses of an animal are impaired by organic diseases such as leukemia, Hodgkin's disease, diabetes, AIDS, etc.

Therapy against other diseases. Modern therapeutic procedures used in some diseases can render an individual more susceptible to infection.

Anatomical defenses associated with tissue surfaces

2. Anatomical Defenses

3.Microbial Antagonism

There are three main ways that the normal flora protect the surfaces where they are colonized:

1) Competition with non-indigenous species for binding (colonization) sites. 2) Specific antagonism against non-indigenous species. Members of the normal flora may produce very specific proteins called bacteriocins which kill or inhibit other (usually closely-related) species of bacteria.3) Nonspecific antagonism against non-indigenous species. The normal flora produce a variety of metabolites and end products that inhibit other microorganisms. These include fatty acids (lactate, propionate, etc.), peroxides and antibiotics.

Enterococcus faecalis, also classified as Streptococcus faecalis. Occasionally there is invasion of the host by the normal flora, as evidenced by this blood culture.

4.Antimicrobial Substances in Host Tissues

Substance Common Sources Chemical Composition

Activity

Lysozyme Serum, saliva, sweat, tears Protein Bacterial cell lysis

Complement Serum Protein-carbohydrate lipoprotein complex

Cell death or lysis of bacteria; participates in inflammation

histones, ß-lysins and other cationic proteins

Serum or organized tissues Proteins or basic peptides

Disruption of bacterial plasma membrane

Lactoferrin and transferrin

Body secretions, serum, organized tissue spaces

Glycoprotein Inhibit microbial growth by binding (withholding ) iron

Peroxidase Saliva, tissues, cells （ neutrophils)

Protein Act with peroxide to cause lethal oxidations of cells

Fibronectin Serum and mucosal surfaces Glycoprotein Clearance of bacteria (opsonization)

Interferons Virus-infected cells, lymphocytes Protein Resistance to virus infections

Interleukins Macrophages, lymphocytes Protein Cause fever; promote activation of immune system

The complement cascade, precipitated by certain antigen-antibody reactions (classical pathway) or by bacterial polysaccharides (alternative pathway), leads to four principal antimicrobial effects: 1. phagocytes are attracted to the site ; 2. inflammatory agents are produced and/Or released from cells ; 3. microbes are opsonized to enhance uptake by phagocytic cells ;4. bacteria are lysed in the presence of lysozyme.

Complement

5. Inflammation

Inflammation is necessary for the proper functioning of all the host defenses, because it focuses all circulating antimicrobial factors on the site of infection. These include phagocytes, lymphocytes, antibodies, complement and other antimicrobial components of plasma.

(1) The inflammatory response is triggered by pathogen invasion or tissue injury.

(2) The increased acidity activates an extracellular enzyme kallikrein which in turn activates bradykinin.

(3a) Bradykinin binds to receptors on the capillary walls opening junctions between cells to allow leakage of plasma components.

(3b) Bradykinin also binds to mast cells of the connective tissue that are associated with the small vessels of most tissues.

Phagocytosis by a Macrophage.

MacrophageMacrophage

6.Phagocytic Defenses

Immune Defense against Bacterial Pathogens:Adaptive or Acquired Immunity

The immunological System

Organs comprising the immune system

Bone Marrow

T-cells mature in the thymus

Spleen

Lymph glands

B-cells and T cells

T-cells

Three important features of an immunological response are:

1. Specificity. An antibody or reactive T-cell will react specifically with the antigen that induced its formation; it will not react with other antigens.

2. Memory. The immunological system has a "memory". Once the immunological response has reacted to produce a specific type of antibody or reactive T-cell, it is capable of producing more of the antibody or activated T-cells rapidly and in larger amounts.

3. Tolerance. An animal generally does not undergo an immunological response to its own components. The animal is said to be tolerant to self-antigens. Tolerance is brought about in a number of ways, but basically the immunological system is able to distinguish "self" antigens from "non-self" antigens.

Primary and Secondary Immunological Responses. Following the first exposure to an antigen the immune response develops gradually over a period of days, reaches a low plateau within 2-3 weeks, and usually begins to decline in a relatively short period of time. When the antigen is encountered a second time, a secondary (memory) response causes a rapid rise in the concentration of antibody, reaching a much higher level in the serum, which may persist for a relatively long period of time.

AMI

Exercises:

1. What are the two groups of defense mechanisms of the body against foreign or harmful agents? What is the difference between them?

2. What are the categories of innate immunity?

3.What are the important features of an immunological response?

4.How do antibodies work to prevent the infections? 5. What are the categories of adaptive immunity?